Imidazole is an important five-membered nitrogen-containing heterocyclic compound. Among the numerous heterocyclic compounds, imidazole and its derivatives are regarded as a unique and multifaceted scaffold material due to their diverse applications in industrial, organic and pharmaceutical chemistry. Imidazoles interact in different ways with many therapeutic targets, enzymes and receptors in biological systems and thus exhibit a wide range of biological activities. In particular, several imidazoles can be used as clinical drugs to treat various types of cancer with high therapeutic efficacy. Furthermore, imidazoles are one of the most critical segments in the field of anti-covid-19 virus drug discovery due to their ability to interact with active targets in living systems.
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The Journal of Medicinal Chemistry recently publishes an article titled, “Discovery of Clinical Candidate PF-06648671: A Potent γ-Secretase Modulator for the Treatment of Alzheimer’s Disease”. Amyloid β-peptide (Aβ) accumulation is one of the key hallmarks of Alzheimer’s disease (AD). γ-secretase cleaves the amyloid precursor protein (APP) into pathologically relevant Aβs, and has been widely studied as a potential target for the treatment of AD.
Pfizer‘s PF-06648671 is a Gamma secretase modulator (GSM) targeting APP processing. It is found to have excellent central exposure in human and robust reduction of amyloidogenic forms (Aβ42) in cerebrospinal fluid (CSF).
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